Human and animal health can be adversely affected by many microorganisms, including bacteria, yeasts, viruses, fungi, mold, and protozoa. Human and animal contact with microorganisms is known to cause a wide variety of diseases, illnesses, and ailments.
It is well known that the washing of hard surfaces (e.g. food preparation surfaces and surgical room equipment), food (e.g. fruits and vegetables), and skin (e.g. hands) with soap and water, can remove many microorganisms from those surfaces. Removal of microorganisms by hand washing with soap is largely due to a combination of the surfactancy of the soap and the mechanical action of the washing procedure. Because washing with soap is effective at removing a substantial number of microorganisms already present, but has only a minimal, if any, lasting or persistent effect on microorganisms that subsequently come into contact with the already washed hands, it is often recommended that people wash their hands frequently in order to reduce the spread of viruses, bacteria, and other microorganisms. Compliance with this recommendation is important for an individual's personal health and hygiene, but is especially important for individuals working in the health and food industries.
Antimicrobial cleansing products for the removal of microorganisms from surfaces, including skin, are available in a variety of types. The most common types utilized for personal hygiene and by personnel working in the health and food industries, include those containing soaps and those containing alcohol.
Traditional rinse-off disinfectant products, such as detergents and soaps, are generally effective at reducing the number of microorganisms present on a surface when proper procedures are employed. For example, Dial® liquid soaps containing triclosan, when used for hand washing, have been shown to reduce the number of bacteria present on the skin by about 2.0-2.5 orders of magnitude (99.0-99.7%) after one 30-second handwash, as measured by standard Health Care Personal Handwash Tests (HCPHWT). In other words, after washing, the washed skin is contaminated with only 0.3%-1.0% of the number of bacteria than was the unwashed skin before the 30-second handwash. Although, when used properly, soaps are capable of removing the majority of bacteria that are present, the persistence of any antimicrobial activity remaining on the surface is minimal, so immediately following hand washing, re-contamination of the hands begins to occur through contact with other contaminated surfaces. In addition, because these traditional rinse-off disinfectant products were developed for use in a washing procedure that uses a substantial amount of water; their use is limited to locations where a substantial amount of water is available.
Another commonly used type of disinfectant are those products containing relatively high levels of alcohol. Alcohol-based disinfectants result in the immediate removal or inactivation of a substantial portion of microorganisms present on the treated surface. Disinfectants based on alcohol, typically ethanol, have an additional advantage as disinfectants because alcohol readily evaporates from the skin at body temperature. Purell® is one example of a skin disinfectant that uses alcohol as the active ingredient. Although properly applied alcohol-based disinfectants are generally effective at removing or destroying bacteria that are present on the skin prior to application, immediately following treatment, re-contamination of treated skin begins to occur through contact with other contaminated surfaces.
Recent studies indicate that alcohol-based sanitizers with less than approximately 60% alcohol content may not be suitable to provide a desirable degree of antimicrobial activity, and alcohol contents above 95% are also less potent because proteins are not denatured easily in the absence of water [“Hand Hygiene Revisited: Another Look at Hand Sanitizers and Antibacterial Soap” SAFEFOOD NEWS—Spring 2004—Vol. 8 No. 3, Colorado State University Cooperative Extension].
Other water-soluble active ingredients have been used in skin disinfectants, instead of, or in combination with, alcohol. Birnbaum et al., (U.S. Pat. No. 6,441,045) disclose a water-soluble quaternary compound for use as a skin disinfectant. Beerse et al., (U.S. Pat. No. 6,217,887) disclose an antimicrobial composition for skin that is meant to be left-on rather than rinsed-off, which contains an antimicrobial active, an anionic surfactant, and a proton-donating agent, in a solution containing up to 98.85% water. Petersen et al., (U.S. Pat. No. 6,627,207) disclose a water-based, quick-drying, gel-type disinfecting composition having a low alcohol content (<30%). Osborne et al., (U.S. Pat. Nos. 5,776,430 and 5,906,808) describe a topical antimicrobial cleanser composition containing 0.65-0.85% chlorhexidine gluconate, or a pharmaceutically acceptable salt, and 50-60% denatured alcohol. Kross (U.S. Pat. No. 5,597,561) discloses water-based, adherent disinfecting composition directed at the prevention of microbial infections, which contains protic acid, a metal chlorite, and a gelling agent. Smyth et al., (U.S. Pat. No. 5,916,568) disclose a quick-drying hand sanitizer composed of alcohol, hydrogen peroxide, and an emollient to help prevent skin irritation. Sawan et al., (U.S. Pat. No. 6,180,584) disclose a disinfectant composition comprised of a polymeric, film-forming material and a metallic biocide in a carrier, which, when applied to a surface, forms a water-insoluble polymeric film on the surface in which the biocide is non-leachably bound to, complexed with, associated with, or dispersed.
Causton et al., (U.S. Pat. No. 5,869,600) disclose the use of water-insoluble, alcohol-soluble copolymers containing some level of quaternary ammonium groups for use as film-forming polymers utilized as antiperspirants.
Other approaches have employed methods that attach reactive silane-based quaternary ammonium compounds to particular substrates via a siloxane bond. For example, AEGIS Environments' product line includes products that utilize polymers of 3-(trimethoxysilyl)propyldimethyloctadecyl ammonium chloride, and are generally applied using alcohol-based solutions. According to product literature, AEM 5700 is 43% 3-(trimethoxysilyl) propyldimethyloctadecyl ammonium chloride in methanol, which can be used to coat the surface of textiles and other objects. This method results in the formation of a permanent covalent bond between the quaternary ammonium antimicrobial compound and the surface being treated. Removal of the applied antimicrobial is thus nearly impossible, even using alcohol-based solvents. Furthermore, the reactive trimethoxysilyl compounds are toxic and not suitable for use on skin.
Sawan (U.S. Pat. No. 6,264,936) describes an antimicrobial material which can be used to form on the surface of a substrate an antimicrobial coating or layer which kills microorganisms on contact. The antimicrobial coating or layer, characterized in the reference as “non-leaching,” is a combination of an organic matrix immobilized on the surface of the substrate to having biocidal metallic materials associated with the matrix. When a microorganism contacts the coating or layer, the biocidal metallic material is transferred to the microorganism in amounts sufficient to kill it. Specifically, the metallic antimicrobial agent used is silver. Although this method purports to provide a “non-leachable” coating, the mere fact that the metallic antimicrobial agent “is transferred” to the microorganism is contrary to the common definition of non-leachable. Furthermore, it is known that although silver and silver salts have very low solubility, the mechanism of antimicrobial activity is dependent on a finite solution concentration of silver ions. Indeed, Sawan later (column 3, line 9) qualifies the above statement to read “substantially low leachables”. In a preferred embodiment of Sawan's patent, the organic material comprises a polyhexamethylene biguanide polymer which is crosslinked with an epoxide, such as N,N-bismethylene diglycidylaniline, to form a crosslinked network or matrix. This crosslinking step is necessary to prevent dissolution of the matrix. The materials described by Sawan generally require a curing step, generally in the range of 80° to 120° C., which is unsuitable for many substrates, particularly human skin. Furthermore, the preferred organic matrix polymer (polyhexamethylene biguanide) is known to be toxic to human cells in high concentrations (see U.S. Pat. No. 6,369,289 B1). The use of silver as an antimicrobial agent also incurs some undesirable effects. One disadvantage to this approach is that certain bacteria have been able to develop resistance to silver. (Silver S., “Bacterial silver resistance: molecular biology and uses and misuses of silver compounds.” FEMS Microbiology Reviews, 2003; 27:341-353). Another disadvantage to this approach is that diffusing silver may be able to enter the wound and may potentially stain the skin. An additional disadvantage of silver is the high cost of the raw material. Similar approaches are described in U.S. Pat. Nos. 6,180,584; 6,126,931; 6,030,632; 5,869,073, 5,849,311; and 5,817,325.
There is a need for improved means and methods for disinfecting surfaces, not only for improved personal hygiene, but also to reduce potential sources of contamination in both health and food industries. With currently used non-persistent disinfectants, personnel in the health industry (e.g. doctors, nurses, and patients) and the food industry (e.g. food handlers, food preparers, cooks, and servers) must apply a disinfectant, such as soap, to their skin several, and sometimes 20 or more times, a day. Consequently, there exists a need, for personal hygiene and hygiene within the health and food industries, for a disinfectant that can effectively sanitize a surface and persist actively on that surface to combat microorganisms that subsequently come into contact with the treated surface.
The need for an effective, persistent surface disinfectant is felt in all aspects of the health industry. It is an aspect of the current invention that the invention would be useful to disinfect skin prior to surgery, injection, phlebotomy, and catheter insertion. Microorganisms present a threat to the health and safety of patients whenever the skin is penetrated, broken, or breached. For example, such pathogens may be a hazard during surgical procedures. Without adequate disinfection of the incision site prior to surgery, microorganisms present on the skin gain access to the incision during or following surgery and cause infection. To prevent such infections, it is critical to disinfect the incision site prior to surgery with a disinfectant that possesses a high antimicrobial activity and a broad spectrum of action. Since surgical procedures can last for many hours, it is also important that the initial disinfection of the incision site persists and provides sustained antimicrobial activity for an extended period of time. In the United States, the Food and Drug Administration requires that a pre-surgical skin disinfectant be capable of reducing the number of flora on dry skin areas, such as an abdomen, by at least 2.5 orders of magnitude or to levels that are too low for reliable quantification (less than about 25 cfu/cm2). On moist skin, such as inguinal areas, the disinfectant must reduce the initial bacterial population by a minimum of 3.2 logs (1.5×103 cfu/mL) and be able to maintain this level for at least four hours.
The need for an effective, persistent, and durable surface disinfectant is also felt in all aspects of the food industry, including food collection (e.g. sanitation of cow teats), food processing (e.g. slaughterhouses), food packaging (e.g. fish canneries), and food distribution (e.g. restaurants and food stores). It is an embodiment of the current invention that the composition would be useful wherever a person has food handling responsibilities and particularly useful wherever proper hygiene is made difficult because the same individual has both food handling and money handling responsibilities (e.g. deli shop cashiers and wait staff).
The ability of many organisms to develop resistance to antimicrobial compounds is a serious problem. Reports of rampant infections from organisms such as methacillin-resistant Staph. aureus (MRSA) abound in the news media. Such resistance is known to occur for many antibiotics, as well as for metal-based systems (such as silver). Quaternary ammonium compounds, on the other hand, do not promote development of resistant organisms.